Therapeutic angiogenesis, the desirable growth of new blood vessels, holds promise for stopping and even reversing the degenerative processes associated with coronary vascular disease, thus reducing morbidity and death in about 14 million Americans. Gene transfection ofphVEGF(165) DNA plasmid has been shown to be an effective means of stimulating new blood vessel growth and obtaining therapeutic effect in patients with peripheral limb vascular disease and ischemic heart disease. However, safer and more effective methods for in vivo gene transfection are needed. PharmaSonics has demonstrated that ultrasound treatment of skeletal muscle, which has been injected with naked DNA plasmid, increases reporter gene expression by about 24 times over that obtained without ultrasound treatment. We have also demonstrated in an ischemic hindlimb rabbit model that, when ultrasound mediated gene transfection is used. DNA dosage can be reduced to 1/5 that needed without ultrasound, and still obtain comparable new blood vessel growth. In this Phase I application, PharmaSonics is requesting funding to conduct experiments aimed at identifying an optimal set of gene transfection parameters for safely producing angiogenesis in heart muscle. PROPOSED COMMERCIAL APPLICATIONS: The demand for a therapy that can safely stimulate local new blood vessel growth in the diseased hearts of 14 million Americans is self evident.